Top-Down Crawl: a method for the ultra-rapid and motif-free alignment of sequences with associated binding metrics
Brendon H Cooper1, Tsu-Pei Chiu1, Remo Rohs1,2
1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Summary:
Several high-throughput protein-DNA binding methods currently available produce highly reproducible measurements of binding affinity at the level of the k-mer. However, understanding where a k-mer is positioned along a binding site sequence depends on alignment. Here, we present Top-Down Crawl (TDC), an ultra-rapid tool designed for the alignment of k-mer level data in a rank-dependent and position weight matrix (PWM)-independent manner. As the framework only depends on the rank of the input, the method can accept input from many types of experiments (protein binding microarray, SELEX-seq, SMiLE-seq, etc.) without the need for specialized parameterization. Measuring the performance of the alignment using multiple linear regression with 5-fold cross-validation, we find TDC to perform as well as or better than computationally expensive PWM-based methods.
Availability And Implementation:
TDC can be run online at https://topdowncrawl.usc.edu or locally as a python package available through pip at https://pypi.org/project/TopDownCrawl.
Supplementary Information:
Supplementary data are available at Bioinformatics online.
